Kavapyrones

Jussofie A, Schmiz A, Hiemke C. Kavapyrone enriched extract from Piper methys-ticum as modulator of the GABA binding site in different regions of rat brain. Psychopharmacology (Berl) 1994 116 469-474. 

The pharmacologically active chemicals most studied from the kava plant are collectively called kavapyrones or kavalactones (referred to here as kavalactones) (figure 6.5). Some of the principal kavaactones are kavain, dihydrokavain, yangonin, 11-methoxy-yangonin, methysticin, and dihydromethysticin (Lebot et al. 1997 Boonen et al. 1997). The concentrations of kavalactones vary across different parts of the plant kavain and dimethoxyyangonin are more concentrated in the rootstalk, but dihy-... 

Neither an acute dose of dihydromethysticin (100 mg/kg) or chronic doses of ( )-kavain altered levels of dopamine, serotonin, or their metabolites in the striatum and cortex of rats (Boonen et al. 1998). However, kavalactones have complex and mixed effects on monoamine levels in the nucleus accumbens, depending both on which kavapyrone was... 

The exact mechanism of action is unclear, but it is thought that kavapyrones may act in the amygdala, producing a tranquilizing and muscle relaxant effect. 

Kava may be effective for the short-term treatment of anxiety. A number of small trials have shown extracts, standardized to 70% kavapyrones, to be significantly and consistently more effective than placebo. Additional studies suggest that kava acts centrally as a muscle relaxant and likely has neuroprotective and nonopioid analgesic properties. 

Kava preparations are frequently standardized to 30 to 70% kavapyrones. Doses of 100 mg (70% kavapyrones) three times daily are often used for anxiety. Kava is sometimes drunk as a tea (2-4 g of root placed in 150 mL of hot water followed by straining). Treatment may take several weeks to be fully effective, but should be limited to no more than 3 months of drug administration. 

Kavapyrones seem to be the therapeutically active constituents. Kava appears to influence a number of monoamine, amino acid, and neuropeptide transmitters in the CNS. Animal studies suggest that kava activates mesolimbic dopaminergic neurons (e.g., in the nucleus accumbens) while also altering 5-HT levels in various brain regions (Baum et ah, 1998). Kava may also act as a reversible MAO inhibitor and a noradrenergic reuptake inhibitor (Uebelhack et ah, 1998). 

Baum, S.S., Hill, R., and Rommelspacher, H. (1998) Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Prog Neuropsychopharmacol Biol Psychiatry 22 1105-1120. 

Haberlein H, Boonen G and Beck M-A (1997) Piper methysticum enantiomeric separation of kavapyrones by high performance liquid chromatography. Planta Med 63, 63-65. 

Extracts of the kava root contain both lipophilic and hydrophilic components. The active constituents of kava are referred to as kavalactones or kavapyrones. The active enolides and dienolides are thought to be kawain (kavain), methysticin, and yangonin. 

Daidzein (= 4,7-Dihydroxyisoflavone) (isoflavone) Desmethoxyyangonin (phenolic-derived dienolide lactone, kavapyrone)... 

Teschke, R. Kava, kavapyrones and toxic liver injury. Z. Gastroenterol. 2003 41 395-404... 

Kava has been associated with toxic Uver damage in six cases reported from Switzerland (12). In one patient, the Uver damage was so extensive that Uver transplantation became necessary. Histological data from four patients were consistent with an allergic mechanism. In several cases, other medications with hepatotoxic potential had been taken concurrently. Symptoms generaUy occurred at between 3 weeks and 4 months and involved daily doses that contained kavapyrones 60-210 mg. Most instances involved acetone extracts. The leading kava extract, Laitan, was subsequently withdrawn from the Swiss market. 

Davies LP, Drew CA, Duffield P, Johnston GAR, Jamieson DD. Kavapyrones and resin studies on GABAA, GABAB, and benzodiazepine binding sites in rodent brain. Pharmacol Toxicol 1992 71 120-126. 

Kava is an attractive shrub (Figure 1.1) that is propagated vegetatively, as are most of the traditional Pacific crops. The active principles are a group of psychoactive chemicals called kavalactones or kavapyrones (Chapter 5), which are concentrated mostly in the rhizome and roots, and in other parts of the plants to a lesser extent. The desired physiological effects are obtained by ingesting the active compounds present in cold-water infusions of ground, macerated, pounded, or sometimes chewed kava stumps and roots. 

Boonen, G., Beck, M.A. and Haberlein, H. (1997) Contribution to the quantitative and enantio-selective determination of kavapyrones by high performance liquid chromatography on ChiraSpher NT material.of Chromatography B, 703, 240-244. 

Boonen, G. and Haberlein, H. (1998) Influence of genuine kavapyrone enantiomers on the GABA binding site. Planta Medica, 64, 504—506. 

Davies, L.P., Drew, C.A., Duffield, P., Johnston, G.A.R. and Jamieson, D.D. (1992) Kavapyrones and resin Studies on GABA, GABAg and benzodiazepine binding sites in rodent brain. 

Janec2ko, Z. and Podolak, I. (2000) Quantitative analysis of kavapyrones in kava-kava (Piper methysticum Forst.) with computer program Chroma . Phytomedicine, 7(Suppl. II), 80. 

Seitz, U., Schiile, A. and Gleitz, J. (1997a) [ H -Monoamine uptake inhibition properties of kavapyrones. Planta Medica, 63, 548—549. 

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